title: Spinocerebellar ataxia type 15: diagnostic assessment, frequency, and phenotypic features.
abstract: BACKGROUND
  To guide time- and cost-efficient analyses of the increasing number of autosomal-dominant spinocerebellar ataxia genes (SCAs), more information about frequency distributions, phenotypic characteristics and optimal diagnostic strategies is warranted.
  
  
  OBJECTIVE
  To assess the prevalence and phenotypic spectrum of SCA15 and to confirm multiplex ligation-dependent probe amplification (MLPA) as a robust and efficient strategy for routine molecular diagnosis.
  
  
  METHODS
  Fifty-six German SCA families negative for common repeat expansions were screened for ITPR1 deletions by MLPA. Samples with conspicuous MLPA data were additionally assessed by high-density single nucleotide polymorphism (SNP) array to confirm MLPA results and further determine the size of deletions. The phenotype of patients harbouring ITPR1 deletions was characterised by standardised clinical, electrophysiological and imaging assessment.
  
  
  RESULTS
  SCA15 accounted for 8.9% (5/56) of SCA families negative for common SCA repeat expansions. All deletions detected by MLPA were confirmed by SNP array. One of the ITPR1 deletions preserved exons 1 and 2 in the 5' prime UTR of the ITPR1 gene. All patients with SCA15 (n=10) presented with slowly progressive cerebellar ataxia and vermal cerebellar atrophy, while clinical and electrophysiological signs of extracerebellar affection were mild and more variable.
  
  
  CONCLUSIONS
  SCA15 is the most common non-trinucleotide repeat SCA in Central Europe. Screening for ITPR1 deletions should be considered in patients with slowly progressive SCA, vermal cerebellar atrophy and prominent tremor after excluding common SCA repeat expansions. Promoter and exon 2 of ITPR1 may be preserved from the deletion in some cases of SCA15.
authors.affiliation: Department of Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, D 72076 Tübingen, Germany.
authors.forename: Matthis
authors.initials: M
authors.lastname: Synofzik
authors.forename: Christian
authors.initials: C
authors.lastname: Beetz
authors.forename: Claudia
authors.initials: C
authors.lastname: Bauer
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Elena
authors.initials: E
authors.lastname: Sanchez-Ferrero
authors.forename: Tanja
authors.initials: T
authors.lastname: Schmitz-Hübsch
authors.forename: Ullrich
authors.initials: U
authors.lastname: Wüllner
authors.forename: Thomas
authors.initials: T
authors.lastname: Nägele
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
mesh_terms: D000328:Adult; D000483:Alleles; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005820:Genetic Testing; D005838:Genotype; D005858:Germany; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics; D008297:Male; D021141:Nucleic Acid Amplification Techniques; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D020754:Spinocerebellar Ataxias / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*
chemical_list: C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors